Pharmacokinetics of lithium in rat brain regions by spectroscopic imaging
Pharmacokinetics of lithium in rat brain regions by spectroscopic imaging
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DOI：
10.1016/j.mri.2005.07.007
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发表时间：
2005-10-01
影响因子：
2.5
通讯作者：
Lyon, M
中科院分区：
文献类型：
--
作者：
Ramaprasad, S;Ripp, E;Lyon, M
锂（Li）及其盐已被证明是双相情感障碍急性和预防性治疗中最有效的药物。确切的分子机制和特定的目标区域占其情绪稳定的效果仍然未知。Li在活体脑中的分布及其区域药代动力学特性的知识在定位其在脑中的作用中具有价值。目前尚未获得人脑不同解剖区域的药代动力学测量结果。用原子吸收法对大鼠脑亚体积进行了有限的药代动力学测定。然而，在药物发挥其有益作用的脑的不同区域中估计药代动力学的非侵入性方法将允许在接受Li治疗的患者的研究中使用这种方法。早期对大鼠脑区的Li-7 MR研究提供了全脑的初步药代动力学信息。利用Li-7磁共振波谱成像（SI）技术，我们最近已经证明了在治疗剂量下，Li在大鼠脑区的分布。在这里，我们报告的可行性，局部药物动力学测量的脑区磁共振SI技术。我们的研究结果表明，李是最活跃的一个区域，从前扣带皮层和纹状体的尾侧中脑，最大的活动，包括视前区和下丘脑区域。在前额皮质中观察到一些活动，但在小脑和后脑脑干区域中仅观察到极少量的活动。(C)2005年爱思唯尔公司All rights reserved.
Lithium (Li) and its salts have been demonstrated to be the most effective drug in both acute and prophylactic treatment of bipolar disorder. The exact molecular mechanisms and particular target regions accounting for its mood-stabilizing effect remain unknown. Knowledge of Li distribution and its regional pharmacokinetic properties in the living brain is of value in localizing its action in the brain. Pharmacokinetic measurements in different anatomical regions of the human brain are not yet available. Limited pharmacokinetic measurements in rat brain subvolumes have been performed using atomic absorption technique. However, a noninvasive way of estimating the pharmacokinetics in different regions of the brain where the drug exerts its beneficial effects would allow such methods to be used in the stud), of patients undergoing Li therapy. Earlier Li-7 MR studies on rat brain regions have provided preliminary pharmacokinetic information from the whole brain. Using Li-7 MR spectroscopic imaging (SI) technology, Li distribution in brain regions of the rat at therapeutic dosages has been recently demonstrated by us. Here we report feasibility of local pharmacokinetic measurements on brain regions obtained by magnetic resonance SI technology. Our results suggest that Li is most active in a region stretching from the anterior cingulate cortex and striatum to the caudal midbrain, with greatest activity including the preoptic area and hypothalamic region. Some activity was seen in prefrontal cortex, but only minimal amounts in the region of the cerebellum and metencephalic brainstem. (C) 2005 Elsevier Inc. All rights reserved.